Pain describes a sensation affecting one or more parts of a human or animal body, resulting in distress and a desire to eliminate or mitigate the sensation and/or its source. According to the definition provided by the International Association for the Study of Pain, “[p]ain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage” (see, International Association for the Study of Pain: Pain Definitions,” Retrieved 12 Jan. 2015, derived from Bonica, “The need of a taxonomy,” Pain; 6(3):247-8. doi:10.1016/0304-3959(79)90046-0. PMID 460931) (1979).
5′ adenosine monophosphate-activated protein kinase, or “AMPK,” is an enzyme that plays a role in cellular energy homeostasis (see, e.g., http://en dot wikipedia dot org/wiki/AMP-activated_protein_kinase). AMPK is expressed in various types of tissue, including the liver, brain, and skeletal muscle. AMPK activation results in the stimulation of hepatic fatty acid oxidation and ketogenesis, inhibition of cholesterol synthesis, lipogenesis, and triglyceride synthesis, inhibition of adipocyte lipolysis and lipogenesis, stimulation of skeletal muscle fatty acid oxidation and muscle glucose uptake, and modulation of insulin secretion by pancreatic beta-cells (supra, and Winder, et al., “AMP-Activated Protein Kinase, a Metabolic Master Switch: Possible Roles in Type 2 Diabetes,” Am. J. Physiol. 277 (1 Pt 1): E1-10. PMID 10409121, July 1999). Various research efforts have indicated a promising role for AMPK activation in the mitigation of pain, including neuropathic pain and nociceptive pain (see, Price, et al., “AMPK: An Emerging Target for Modification of Injury-Induced Pain Plasticity,” Neurosci. Lett.; 557 Pt A:9-18. doi: 10.1016/j.neulet.2013.06.060. Epub 2013 Jul. 3 2013 Dec. 17, and, Tillu, et al., “Resveratrol Engages AMPK to Attenuate ERK and mTOR Signaling in Sensory Neurons and Inhibits Incision-Induced Acute and Chronic Pain,” J. Mol. Pain 8:5. doi: 10.1186/1744-8069-8-5, 2012 Jan. 23). In this research, the topical administration of AMPK activators, also called agonists, e.g., resveratrol, has shown efficacy in mitigation of pain in an animal model (rodents).